Methods for providing optimized neurostimulation

ABSTRACT

Disclosed herein are methods for neurostimulation therapy for spinal cord injury. More particularly, the present invention relates to methods for neurostimulation therapy for spinal cord injury. More particularly, the present invention relates to methods for providing multiple independent, simultaneous waveforms in neurostimulation therapy while minimizing or substantially eliminating undesirable interactions between the waveforms.

This application is a divisional of prior application Ser. No.15/752,280, filed Feb. 13, 2018, which was the National Stage ofInternational Application No. PCT/US2016/047535, filed Aug. 18, 2016,which claims the benefit of U.S. Provisional Patent Application No.62/206,937, filed 19 Aug. 2015, all of which are incorporated herein byreference.

FIELD OF THE INVENTION

Embodiments of the present invention relate to methods forneurostimulation therapy for spinal cord injury. More particularly,embodiments of the present invention relate to methods for providingmultiple independent, simultaneous waveforms in neurostimulation therapywhile minimizing or substantially eliminating undesirable interactionsbetween the waveforms.

BACKGROUND

Serious spinal cord injuries (SCI) result in partial (incomplete) orsubstantially complete loss of sensory motor function below the level ofthe spinal lesion. For individuals with incomplete loss of motorfunction, substantial recovery of standing and stepping recovery hasbeen demonstrated with task specific physical rehabilitation training.Recently, task specific physical rehabilitation training has beencombined with epidural stimulation (ES) of the spinal cord in patientswith incomplete and complete motor paralysis. High density epiduralstimulating electrode arrays can provide spatially selective stimulationto regions of the spinal cord to facilitate or cause muscle movement.

SCI and other conditions may benefit from the delivery of stimulusintended to enable or excite multiple neurological responses using animplantable neurostimulator. A targeted neurological function, such asblood pressure, may respond to a particular electrical stimulus orwaveform at a specific location, amplitude, frequency, pulse width or acombination thereof. Other functions, such as muscle flexon, may requirea different waveform to produce the desired response. For situationswhere multiple neurological functions need to be stimulated at the sametime, the different stimulus signals may interfere and prevent thedesired responses or even cause an undesired and potentially dangerousoverstimulated condition.

The circuit shown in FIG. 1 is a simplified model of four electrodesbeing stimulated using two different waveforms for neurostimulation. Afirst waveform connects to electrode pair 4 and 3, while a secondwaveform connects to electrode pair 2 and 1. Node R is common to allelectrodes, since all electrodes are in a common conductive medium,e.g., tissue and fluid. Interactions between each pair of electrode setsor waveforms can occur when electrodes are not isolated from connectingcircuits. These coupled interactions between waveforms with overlappingpulses can add constructively or destructively to each other, dependingupon if each pulse is in the charging or discharging phase. Moreover,this situation of overlapping pulses from multiple and simultaneouswaveforms will result, at minimum, in undesired stimuli and could resultin larger than intended and potentially dangerous stimuli fromconstructive interference in scenarios where the overlapping pulses addtogether. Overlapping pulses can also interfere destructively, whichwill limit the expected waveform amplitude delivered to the nerves.Overlapping pulses can also make charge balancing very complicated, as aclinician may not know the exact behavior of interactions betweenpulses. This scenario of overlapping pulses may occur routinely if eachwaveform is allowed to independently vary in frequency and pulse width.

The common approach in the industry for managing interaction betweenwaveforms is to not allow overlap of stimulus pulses between electrodepairs or sets. One product, the Precision Spectra™ stimulator offered byBoston Scientific, allows for independent variation of the frequency andpulse width for up to four simultaneous waveforms. The product, asunderstood by the inventors, manages interactions between waveforms bydetecting waveform overlap, defined as pulses within 3 milliseconds (ms)of each other, and if detected, automatically delaying one the pulses by3 ms. This approach has several shortcomings, including (1) no userunderstanding of the effect this pulse delay has on the frequency changeof the waveform—the more overlapping pulses are delayed, the greater theeffect on the frequency change of the waveform—or even which waveformwas affected, (2) no user control or feedback, as the waveformmanagement is performed autonomously by hardware, (3) no pre-processingof the phase relationship between waveforms to minimize the number ofoverlap occurrences, (4) no option to select the length of the delay orselect which of the overlapping pulses receives the delay, (5) no optionto “blank” or refrain from emitting the overlapping pulse at aparticular instant in time, (6) no ability to prioritize which of theoverlapping waveforms will be blanked or phase shifted, (7) no abilityto change the recharge width of the pulse, (8) no ability to change theshorting width of the pulse, and (9) no ability to accommodate globalshorting windows. The assembly and delivery of sophisticated stimulationpatterns while minimizing undesirable interactions between waveformsremains a challenge.

SUMMARY

Disclosed herein are methods for minimizing undesirable interactionsbetween waveforms, particularly in neurostimulation therapy for spinalcord injury. Methods include modifying characteristics of independent,simultaneous waveforms with overlapping pulses, and hardware-basedsolutions for minimizing or substantially eliminating interactionsbetween pulses.

It will be appreciated that the various apparatus and methods describedin this summary section, as well as elsewhere in this application, canbe expressed as a large number of different combinations andsubcombinations. All such useful, novel, and inventive combinations andsubcombinations are contemplated herein, it being recognized that theexplicit expression of each of these combinations is unnecessary.

BRIEF DESCRIPTION OF THE DRAWINGS

A better understanding of the present invention will be had uponreference to the following description in conjunction with theaccompanying drawings.

FIG. 1 is a schematic of an exemplary circuit for providing twosimultaneous and independent waveforms.

FIG. 2 is a schematic displaying pulses of waveforms W1 and W2 a andphase optimized waveform W2 b. Individual pulses are depicted as lines,with dotted lines depicting pulse collisions between W1 and W2 a whichare avoided in phase optimized waveform W2 b.

FIG. 3 is a schematic displaying pulses of waveform W1 and frequencyoptimized waveform W2. Individual pulses are depicted as lines, withdotted lines depicting pulse collisions avoided by frequencyoptimization of W2.

FIG. 4 is a chart depicting five simultaneous waveforms, with optimizedand non-optimized versions of the waveforms superimposed.

FIG. 5A is a chart depicting three simultaneous waveforms generated by aneurostimulator with (top) a frequency of 55 Hz and a pulse width of 200μs, (middle) a frequency of 33 Hz and a pulse width of 750 μs, and(bottom) a frequency of 25 Hz and a pulse width of 1000 μs.

FIG. 5B is a chart depicting pulse collisions between the waveforms ofFIG. 5A, with the top line displaying collisions between all threewaveforms, the next lower line displaying collisions between the 33 Hzand 55 Hz waveforms, the next lower line displaying collisions betweenthe 25 Hz and 55 Hz waveforms, and the bottom line displaying collisionsbetween the 25 Hz and 33 Hz waveforms.

FIG. 6A is a chart depicting the three waveforms of FIG. 5A after phaseoptimization of the 33 Hz waveform.

FIG. 6B is a chart depicting pulse collisions between the waveforms ofFIG. 6A, with the top line displaying collisions between all threewaveforms, the next lower line displaying collisions between the 33 Hzand 55 Hz waveforms, the next lower line displaying collisions betweenthe 25 Hz and 55 Hz waveforms, and the bottom line displaying collisionsbetween the 25 Hz and 33 Hz waveforms.

FIG. 7A is a chart depicting the three waveforms of FIG. 5A after pulsewidth optimization of the three waveforms.

FIG. 7B is a chart depicting pulse collisions between the waveforms ofFIG. 7A, with the top line displaying collisions between all threewaveforms, the next lower line displaying collisions between the 33 Hzand 55 Hz waveforms, the next lower line displaying collisions betweenthe 25 Hz and 55 Hz waveforms, and the bottom line displaying collisionsbetween the 25 Hz and 33 Hz waveforms.

FIG. 8A is a chart depicting the three waveforms of FIG. 5A after pulsewidth optimization and phase optimization of the three waveforms.

FIG. 8B is a chart depicting pulse collisions between the waveforms ofFIG. 8A, with the top line displaying collisions between all threewaveforms, the next lower line displaying collisions between the 33 Hzand 55 Hz waveforms, the next lower line displaying collisions betweenthe 25 Hz and 55 Hz waveforms, and the bottom line displaying collisionsbetween the 25 Hz and 33 Hz waveforms.

FIG. 9A is a flowchart depicting an exemplary method for optimizingwaveforms.

FIG. 9B is a flowchart depicting an exemplary phase optimizationprocess.

FIG. 10 is a schematic of an exemplary circuit including two separateand isolated power sources.

FIG. 11A depicts a schematic of an electrode array with two independentpower supplies.

FIG. 11B depicts an oscilloscope trace from activation of the firstelectrode array shown in FIG. 11A.

FIG. 11C depicts a schematic of a second electrode array with twoindependent power supplies.

FIG. 11D depicts an oscilloscope trace from activation of the secondelectrode array shown in FIG. 11C.

FIG. 12A depicts a schematic of a third electrode array.

FIG. 12B depicts a first oscilloscope trace from activation of the thirdelectrode array shown in FIG. 12A.

FIG. 12C depicts a second oscilloscope trace from activation of thethird electrode array shown in FIG. 12A.

FIG. 13 depicts a series of electrode arrays designated X, S1, S2 and I.

FIG. 14 includes four panels depicting oscilloscope traces fromactivation of electrode arrays X, S1, S2 and I shown in FIG. 13.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

For the purposes of promoting an understanding of the principles of theinvention, reference will now be made to selected embodimentsillustrated in the drawings and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of the invention is thereby intended; any alterations andfurther modifications of the described or illustrated embodiments, andany further applications of the principles of the invention asillustrated herein are contemplated as would normally occur to oneskilled in the art to which the invention relates. At least oneembodiment of the invention is shown in great detail, although it willbe apparent to those skilled in the relevant art that some features orsome combinations of features may not be shown for the sake of clarity.

Any reference to “invention” within this document herein is a referenceto an embodiment of a family of inventions, with no single embodimentincluding features that are necessarily included in all embodiments,unless otherwise stated. Further, although there may be references to“advantages” provided by some embodiments of the present invention, itis understood that other embodiments may not include those sameadvantages, or may include different advantages. Any advantagesdescribed herein are not to be construed as limiting to any of theclaims.

Specific quantities (spatial dimensions, angles, dimensionlessparameters, etc.) may be used explicitly or implicitly herein, suchspecific quantities are presented as examples and are approximate valuesunless otherwise indicated. Discussions pertaining to specificcompositions of matter are presented as examples and do not limit theapplicability of other compositions of matter, especially othercompositions of matter with similar properties, unless otherwiseindicated.

The present invention comprises methods for minimizing undesirableinteractions between waveforms, particularly in nerve stimulationtherapy for spinal cord injury. In nerve stimulation therapy, anelectrode array comprising a plurality of electrodes disposed on aflexible biocompatible material is provided. Preferably, the electrodescomprise one or more biocompatible metals or alloys, as known in theart. Sets of electrodes within the array generate waveforms, theelectrode array being configured to generate at least two simultaneouswaveforms, each waveform having a frequency, a pulse width, a phase andat least one pulse.

The electrode array and resulting waveforms may be optimized to reduceoverlapping pulses between waveforms by software or hardware-basedsolutions. In some embodiments, waveforms are optimized by at least oneof altering the phase of the waveform, altering the frequency of thewaveform, altering the pulse width of the waveform, delaying a pulse ofthe waveform and blanking a pulse of the waveform.

The first method of waveform optimization is phase optimization. Thismethod uses a computed delay to find the optimal position of waveformsrelative to each other for the purpose of avoiding as many overlappingpulses as possible. Waveforms are assigned a priority and their phase isadjusted to optimize the higher priority waveform first. Referring toFIG. 2, the top waveform (W1) is designated the high priority waveformand remains unchanged. A lower priority waveform, W2, has a designatedphase and collisions (overlapping pulses) between waveforms arepredicted and counted. W2 a shows three collisions with W1, as indicatedby the vertical dashed lines, where pulses from W2 a overlap with pulsesfrom W1. The waveform then has its phase delayed by an increment and thecollisions are recounted in W2 b. The phase delay results in nocollisions between W2 b and W1 in the time period shown. In someembodiments, the delay that results in the fewest number of collisionsis considered the optimized phase delay and can be set to automaticallybe adopted by the system or controlled manually. When a collision doesoccur, the lower priority offending pulse can either be “blanked” oreliminated, or phase shifted forward or backward in time to avoidoverlapping, depending on which option is therapeutically preferable forthe patient. Additional waveforms of lower priority can be testedagainst W1 and the optimized W2 b to obtain the optimal delay for theadditional waveforms.

The steps in this method can be summarized as follows: (1) count thenumber of collisions between two waveforms, W1 and W2, over a period oftime T; (2) delay the lower priority waveform, in this case W2, anincrement and recount collisions in period T; (3) repeat steps 1 and 2until the increment reaches the period of the highest frequency waveformbeing compared; (4) adopt the delay (also referred to as “phase shift”)that results in the lowest number of collisions; and (5) blank specificpulses from the W2 (the lower priority waveform) to remove the collisionin order to produce a corrected W2. In the event that an additionalwaveform is used, steps 1-5 are repeated such that the additionalwaveform is compared to W1 and corrected W2, a phase shift is adoptedfor the additional waveform that minimizes collisions with higherpriority waveforms, and overlapping pulses are blanked to produce acorrected additional waveform. The steps may be repeated as needed forfurther simultaneous waveforms.

A second method of waveform optimization is an alternating frequencyapproach. In this method, the frequency of a lower priority waveform isvaried to avoid overlapping with the higher priority waveform. In someembodiments, the lower priority waveform varies between twopredetermined frequencies to avoid collisions with a higher prioritywaveform. Combining two frequencies on one waveform allows an intervalto form so that no blanking or delayed reset is required. This twofrequency approach eliminates a missing pulse and hence small gaps withno active stimulus.

Referring now to FIG. 3, two waveforms W1 and W2 are frequencyoptimized. In this example, W1 is the higher priority waveform and itsfrequency does not change. In the depicted example, the period of W1 is7x. W2 is a lower priority waveform that is allowed to change betweentwo fixed frequencies with periods 4X and 5X. When a collision iscomputed to occur, represented in FIG. 3 by a dashed line, the otherfrequency is selected. That is, if a pulse overlap is expected to occurwhile maintaining the 4X period, the W2 waveform is transitioned to the5X period prior to the overlap to avoid the collision. Subsequently, ifa collision is estimated to overlap at the 5X period, the waveform istransitioned back to the 4X period. This produces a waveform with twoalternating frequencies. The choice of frequencies may be based on theeffectiveness of the chosen frequencies on neurostimulation, in that asmall frequency change may not be detrimental to therapy, and based onselecting frequencies which correct the timing and minimize the numberof collisions. While this method is primarily designed to avoid pulsecollisions, varying the frequency of a waveform may also be used tointentionally create a desired neurostimulatory response.

The third method for managing waveforms is a charge balance timeoptimization approach. A typical neurostimulation pulse includes a waitperiod (X), charge pulse (1), inter-pulse delay (0.05), a recharge pulse(4), and a shorting period (4). The numbers correspond to the relativelength of that portion of the pulse, with the length of the wait periodbeing variable. The duration of the pulse and subsequent delay, rechargepulse and shorting period are determined by neurological needs and theneed to balance charge on the electrode. In some cases it is possible toshorten pulses or parts of pulses to help eliminate overlap conditionsbetween waveforms. In particular, the charge balance portion of thepulse (i.e., the recharge pulse and shorting period) may be reduced. Forexample, the recharge pulse (also referred to as the recharge period)could be reduced from (4) to (3) and the shorting period from (4) to (2)resulting in an approximate 33% reduction in duration for the activeportion of the pulse. Brief periods of charge balance time optimizationmay be used to allow spacing between pulses from different waveforms andreduce the need to blank a pulse.

The percentage of overlap of two colliding pulses is an indicator as tothe effectiveness of using charge balance time optimization as asolution. Referring now to FIG. 4, the pulse collision between fivesimultaneous waveforms can be reduced by over 90% by just changing theadjustable recharge period from (4) to (1). The recharge period isvisible as the relatively small period of decreased amplitude directlyfollowing each pulse. Decreasing the recharge period increases theavailable time window from only 3.5% to 65% to incorporate globalshorting and to minimize any residual electrode charge. Commercialneurostimulators typically use a recharge pulse length of (4) to amplyensure that charge has been removed from the electrode and to minimizepower consumption. However, the ability to vary the width of therecharge pulse and shorting pulse provides clinicians with tremendousflexibility in managing waveforms to reduce overlaps. For example, asystem may operate in a high power mode with a short recharge pulselength of (1) when managing multiple complex waveforms with long chargepulses and many pulse overlaps, and switch to a low power mode using along recharge pulse length of (4) when managing few waveforms with shortcharge pulses and few pulse overlaps.

A fourth method of managing waveform interactions is by blanking a lowerpriority waveform. In this method, upon detection, calculation orprediction of an overlap of pulses between a higher priority waveformand a lower priority waveform, the pulse of the lower priority waveformis blanked. However, blanking a pulse can result in a small signal voidthat may be undesirable. Another option to blanking an overlapping pulseis to add a pulse to delay the waveform so it can be reset to restartthe waveform in its initial position. This is similar to the twofrequency approach described in the second method. However, in thiscase, the frequency that is produced by the corrected delay occurs forone period and is calculated on a collision by collision basis.

FIGS. 5-8 display the results of these various methods in optimizingthree simultaneous waveforms, one with a frequency of 25 Hz, a secondwith a frequency of 33 Hz, and a third with a frequency of 55 Hz, withrespective pulse widths of 1000 microseconds, 750 microseconds, and 200microseconds. In this example, the 55 Hz waveform is considered thehighest priority waveform. FIG. 5A depicts pulses from the threewaveforms, each with recharge period of 4 and a shorting period of 4.FIG. 5B depicts collisions between pulses from the three waveforms. Inthis unoptimized arrangement, the rate of pulse collisions between the25 Hz and 33 Hz waveforms is 52%, the rate of pulse collisions betweenthe 25 Hz and 55 Hz waveforms is 60% and rate of pulse collisionsbetween the 33 Hz and 55 Hz waveforms is 67%.

FIG. 6A depicts the three waveforms from FIG. 5A after undergoing phaseoptimization. The 33 Hz waveform has been delayed to decrease collisionswith the highest priority waveform, that being the 55 Hz waveform. Thefrequencies, pulse widths, recharge periods and shorting periods remainunchanged. As shown in FIG. 6B, the number of collisions between pulsesin the 55 Hz and 33 Hz waveforms has decreased significantly. In thisphase optimized arrangement, the rate of pulse collisions between the 25Hz and 33 Hz waveforms remains unchanged at 52%, the rate of pulsecollisions between the 25 Hz and 55 Hz waveforms remains unchanged at60% and rate of pulse collisions between the 33 Hz and 55 Hz waveformshas decreased to 33%, a 34% reduction as compared to the unoptimizedarrangement in FIGS. 5A-B. Further reduction of collisions may beachievable by phase optimization of the 25 Hz waveform against the 55 Hzwaveform and the optimized 33 Hz waveform.

FIG. 7A depicts the three waveforms from FIG. 5A after undergoing chargebalance time optimization. The recharge period has been decreased to (1)and the shorting period has been decreased to (0). The frequencies andonset times of the waveforms remain unchanged, as do the pulse widths ofthe charging pulses. As shown in FIG. 7B, the number of collisionsbetween pulses has decreased significantly for all three waveforms. Inthis pulse width optimized arrangement, the rate of pulse collisionsbetween the 25 Hz and 33 Hz waveforms has decreased to 12%, the rate ofpulse collisions between the 25 Hz and 55 Hz waveforms remains hasdecreased to 20% and rate of pulse collisions between the 33 Hz and 55Hz waveforms has decreased to 33%. Further reduction of collisions maybe achievable by phase optimization of the 25 Hz waveform against the 55Hz waveform and the optimized 33 Hz waveform.

FIG. 8A depicts the three waveforms from FIG. 5A after undergoing chargebalance time optimization and phase optimization. The recharge periodhas been decreased to (1) and the shorting period has been decreased to(0) for all three waveforms. In addition, the 33 Hz waveform has beendelayed to decrease collisions with the 55 Hz waveform, and subsequentlythe 25 Hz has been delayed to decrease collisions with the 55 Hz and 33Hz waveforms. The frequencies of the waveforms remain unchanged. Asshown in FIG. 8B, the number of collisions between pulses has decreasedsignificantly for all three waveforms. In this pulse width optimized andphase optimized arrangement, the rate of pulse collisions between the 25Hz and 33 Hz waveforms has decreased to 8%, and all pulse collisionsbetween the 55 Hz waveform and the other two waveforms have beeneliminated. In some embodiments, the remaining overlapping pulsesbetween the 25 Hz and 33 Hz waveforms may be blanked or delayed in thelower priority waveform to eliminate all overlaps.

In some embodiments the priority of waveforms may be changeable. In theexamples depicted in FIGS. 2 and 3, W1 is defined as the high prioritywaveform and thus no alterations such as blanking, phase shift, delay orfrequency shift are applied to that waveform. In practice, it may beadvantageous to change the priority of a waveform based on factors suchas the rate that modifications are occurring to a given waveform, timesince last modification of a given waveform, or implantable pulsegenerator (IPG) commands for particular tasks. For example, a newlyactivated waveform may begin with a high priority, then may reduce inpriority over time. For another example, when a first waveformexperiences a high number of alterations, the system could trigger asecond, higher priority waveform to reduce its priority in order todecrease the number of alterations to the first waveform.

Pulse collisions are typically avoided to isolate patient stimuli andmaintain a balanced charge on neurostimulator electrodes. However, apurposeful pulse collision may be used to determine details about theequivalent circuit of the array or study the impact of field shapes onneuro responses. For this reason it may be desirable to generatecollisions under controlled conditions.

The first four methods of optimization disclosed herein may beimplemented in software controlling an implanted neurostimulator. Insome embodiments, a technical user interface (TUI), such as a generalpurpose computer, or a patient user interface (PUI), such as a portablededicated computing device, a smartphone or other portable computingdevice, run software communicatively coupled to the implantedneurostimulator and capable of adjusting the characteristics ofwaveforms generated by the neurostimulator. In some embodiments, theclinicians initially use the TUI in a clinical setting to evaluate theSCI patients to identify the set of waveforms necessary to generateresponses from the patient, such as standing, leg flexion, legextension, blood pressure control, bladder control, etc. Overlappingpulses often occur when generating multiple simultaneous pulses thathave different frequencies that are not harmonically related to eachother, as shown in FIGS. 5A and 5B.

The optimum set of waveforms and their characteristics (e.g., frequency,amplitude, phase, delay, and pulse width) are unique to each patient.The clinician uses the TUI to identify waveforms needed by a patient toelicit a desired response, such as waveforms stimulating leg muscles toelicit a walking motion, in conjunction with waveforms maintaining thepatient's blood pressure at a safe level. The clinician determines thepriority of the various wave forms based on the patient's physiologicalneeds. For example, waveforms maintaining blood pressure are morecritical to the patient's health than waveforms eliciting a walkingmotion so blood pressure-related waveforms will be designated as higherpriority than walking-related waveforms. These waveforms are thenoptimized using one or more of the methods described above. Once theseoptimized waveforms are determined, they can be transferred from the TUIto the PUI for the patient to activate at the patient's discretion. Inpreferred embodiments, the patient uses the PUI to select what motorresponses, such as standing or walking, or physiological responses, suchas blood pressure control, that he or she wishes to enact, and the PUIinstructs the patient's implanted neurostimulator to enact thepredetermined waveforms to enact such responses in the patient. In apreferred embodiment, PUI is configured such that the patient can onlyrun waveforms optimized by the TUI, and the patient cannot create ormodify waveforms or combinations thereof.

Using the TUI to manage the overlapping pulse waveforms providesclinicians with control over how the overlapping waveforms are modifiedto reduce or eliminate the problem. In some embodiments, the TUI runssoftware is designed to display waveforms and show what percentage ofoverlap exists and where the overlap occurs in time, as shown in FIGS.5-8. The clinician is then presented options as described in methods onethrough four to reduce or eliminate the number of overlapping pulses.Once the waveforms are optimized, they are transmitted from the TUI to abase station, which wirelessly transmits the data to the IPG. In otherembodiments, the first four methods of optimization disclosed herein maybe implemented in the hardware of the neurostimulator such as, byalgorithmic detection of pulse collisions and implementation of methodsto minimize collisions. In such embodiments, unoptimized waveforms aretransmitted to the neurostimulator and a controller, such as amicroprocessor, included in the neurostimulator optimizes the waveformsbefore delivery of electric stimulation to the patient.

FIGS. 9A and 9B provide an embodiment of a method for optimizingwaveforms, with FIG. 9B providing an exemplary initial phase delayoptimization program, as referenced in step 3 in the flowchart of FIG.9A. The exemplary program depicted in FIG. 9B is specific to only theinitial phase delay optimization for minimization of pulse overlaps,and, in other embodiments, significantly more complex programs would beused.

Referring now to FIG. 9A, in initial step 10, a user identifies two ormore waveforms for delivery to a patient, and designates electrodes toprovide the waveforms, setting pulse width, frequency, amplitude,waveform priority, onset and offset times, and other relevant settings.In step 12, the user sets a recharge period for active charge balancefor the activating electrodes and sets a local shorting period forpassive charge balance for the activating electrodes. The rechargeperiod is typically (1), (2) or (4), with (4) being the most commoninitial value of an unoptimized waveform. The shorting period istypically (0), (1), (2) or (4), with (4) being the most common initialvalue of an unoptimized waveform. In step 14, the user performs a phaseoptimization to add a delay to waveforms, apart from the highestpriority waveform, as explained in further detail in connection withFIG. 9B. In step 16, the user reviews the simulated collisions afterphase optimization. If the percentage of pulses colliding is greaterthan a predetermined value, such as greater than 20%, greater than 25%,greater than 30%, or greater than 50%, then optimization is notperformed and the process is begun again using non-identical waveforms.In step 18, pulses on lower priority waveforms which collide with pulseson higher priority waveforms are blanked. In step 20, the optimizedwaveforms are transmitted to the neurostimulator. In certainembodiments, the optimized waveforms are transmitted from the TUI to abase station by a wired or wireless connection, then transmitted by awireless connection between the base station and the neurostimulator. Incertain embodiments, the user is a clinician or other medicalprofessional trained in neurostimulation techniques. In someembodiments, the waveforms are optimized by phase optimization, pulsewidth optimization, frequency optimization, blanking colliding pulses,or a combination thereof. In certain embodiments, the waveforms areoptimized by performing at least two different optimization processes.

FIG. 9B depicts an exemplary phase optimization process for twowaveforms as performed in step 14 of the flowchart shown in FIG. 9A. Thetwo waveforms differ in frequency, and are designated as the highfrequency waveform and the low frequency waveform. In step 22, thewavelength of the high frequency waveform is calculated using techniquesknown in the art (in signal processing, wavelengths are typicallymeasured in units of time, not distance). In subsequent step 24, a firstcounting variable is assigned a value of zero. Subsequent step 26 is aBoolean determination of whether the first counting variable is lessthan the calculated wavelength: if false, the process proceeds to step28 and outputs the optimum shifting position, and if true, the processproceeds to step 30. In step 30, a second counting variable is assigneda value of zero. Subsequent step 32 is a Boolean determination ofwhether the second counting variable is less than the calculatedwavelength: if false, the process proceeds to step 34, and if true, theprocess proceeds to step 36. In step 34, first counting variable isincreased by a first increment, then the process returns to step 26. Instep 36, the onset time of the low frequency waveform is delayed by thesum of the first counting variable and the second counting variable. Insubsequent step 38, the number of pulse collisions between the highfrequency waveform and delayed low frequency waveform is calculated.Subsequent step 40 is a Boolean determination of whether the number ofcollisions calculated immediately prior in step 38 is less than thenumber of previously calculated collisions: if false, the processproceeds to step 42, and if true, the process proceeds to step 44. Instep 42, the second counting variable is increased by a secondincrement, then the process returns to step 32. In step 44, the optimumshifting position (initially set as zero) is defined as the sum of thefirst counting variable and the second counting variable, then theprocess proceeds to step 42 and continues cycling. When the processeventually reaches step 28, increments of shifting ranging from noshifting to shifting the entire wavelength of the high frequencywaveform have been evaluated, and the outputted optimum shiftingposition is the shifting position which resulted in the lowest number ofcollisions.

In some embodiments, the process depicted in FIG. 9B may be repeated tooptimize multiple waveforms. For example, the process may be run a firsttime to optimize a second-highest frequency waveform against a highestfrequency waveform. The process may subsequently be run a second time tooptimize a third-highest frequency waveform against the highest andsecond-highest frequency waveforms. The process may be run additionaltime to optimize still lower frequency waveforms against higherfrequency waveforms until some or all of the simultaneous waveforms in agiven neurostimulation have been optimized. Stepwise evaluationprocesses similar to that shown in FIG. 9B may be used for pulse widthoptimization, frequency optimization and blanking pulses to reduce pulsecollisions.

Embodiments of the present invention relate to hardware-dependentmethods of managing waveform interactions. In a fifth method foroptimization, independent and isolated power supplies are used tocorrect the overlapping pulse issue. Referring now to FIG. 10, anexemplary electrode diagram is shown including two separate and isolatedpower sources, PS1 and PS2, which are connected to the current sourcesby dotted lines. Although the electrodes 1, 2, 3, 4, 5 and 6, share asingle common node R, there is only one connection, so there is noreturn path for current and this stimuli between sections A and B remainisolated. This method requires a separate and isolated power source foreach electrode group containing common frequencies and pulse widths. Inthis example, group A has four electrodes 1, 2, 3 and 4 with a commonfirst frequency and first pulse width, and group B has two electrodes 5and 6 with a common second frequency and second pulse width. In someembodiments, the first and second frequencies are non-identical. Incertain embodiments, the first and second pulse widths arenon-identical. This method depends upon the accuracy of the common nodemodel for the electrode array. If electrodes of section A are in closephysical proximity to electrodes of section B, the accuracy of the modelmay degrade and some interaction between the waveforms, also referred toas “cross talk,” may occur. In some embodiments, undesirable cross talkoccurs when adjacent electrodes are powered by separate and isolatedpower sources. In other embodiments, undesirable cross talk occurs whenelectrodes powered by a separate and isolated power source are locatedwithin 0.5 cm, within 1.0 cm, or within 1.5 cm of electrodes powered byanother separate and isolated power source.

Examples of this fifth method for optimization are shown in FIGS.11A-11D and FIGS. 12A-12C. FIG. 11A depicts an array of electrodeswherein a pair of electrodes at the top of the array, as indicated by agrey oval, are stimulated by a first IPG and another pair of electrodesat the bottom of the array, as indicated by another grey oval, arestimulated by a second IPG. FIG. 11B depicts an oscilloscope trace fromthe bottom electrode pair, which displays no evidence of waveforminteraction from the separate IPG stimulating the top electrode pair. Incontrast, FIG. 11C depicts an array of electrodes including two adjacenttrios of electrodes, each indicated by grey ovals, and each stimulatedby separate IPGs. FIG. 11D depicts an oscilloscope trace from one of thetrios of electrodes. The large peaks in the scope trace represent pulsesfrom the traced electrodes, and the small peaks indicate pulses from theadjacent electrodes. FIGS. 11C and 11D indicate that, even when isolatedpower supplies are used, cross talk can still occur between closelyspaced electrodes.

FIG. 12A depicts an array of electrodes wherein a pair of electrodes atthe bottom of the array and a pair of electrodes at the top of the arrayare stimulated using a single IPG having non-isolated power supplies.FIGS. 12B and 12C depict scope traces from the bottom pair of electrodestaken at two different time points. FIG. 12B shows cross talk betweenthe top and bottom electrode pairs, while FIG. 12C shows no cross talk.Taken as a whole, FIGS. 11A-12C indicate that waveform interactions canbe avoided by stimulating electrodes using independent and isolatedpower supplies when those electrodes are not in close physical proximityto each other.

A sixth method of managing waveform interactions includes the use ofanodes or cathodes at a fixed potential to provide shielding of theelectric field between independent and simultaneous waveforms. Usingcommon ground electrodes physically positioned between stimulationelectrodes to shield and separate the stimulation electrodes caneffectively compare to managing waveform interactions by using isolatedpower supplies. It can minimize the interference of two overlappingpulses from two different stimulation electrodes. Test results show thatthe effectiveness of such shield can compare to the results of usingelectrodes with two isolated power supplies.

Referring now to FIGS. 13 and 14, FIG. 13 depicts five schematicelectrode arrays labeled X, S1, S2, C1 and C2. In each array, current iflows to stimulation cathode electrodes on the left side of the array,and all anodes have equal potential with the ground. Current is measuredin electrodes on the right side of the array, whereby measured currentindicates current leakage between electrodes. Additional anodes servingas ground electrodes are positioned between the stimulation andmeasurement electrodes in arrays S1 and S2 serving as shieldingelectrodes. Additional anodes serving as ground electrodes are alsopresent in arrays C1 and C2, but such additional anodes are notpositioned between the stimulation and measurement electrodes. Noadditional anodes are present in array X. Each array uses a single,non-isolated power supply. FIG. 14 depicts waveforms from oscilloscopemeasurements of arrays S1, S2, C1 and C2. All tests were performed withthe Medtronic Specify™ 5-6-5 electrode array in 1.6 mM buffer solution.In array X, with no shielding electrodes, 3.925 mA of current aregenerated across the 2 electrodes on the left and 1.15 mA are measurableon the 2 electrodes on the right, which evidences current leakage orinteraction of 29% from one side of the electrode array to the other. Inarray S1, 4.636 mA of current are generated across the 2 electrodes onthe left and 0.488 mA are measurable on the 2 electrodes on the right,which evidences a current leakage of 10% in the array including 4shielding electrodes. In array S2, 4.312 mA of current are generatedacross the 2 electrodes on the left and 0.575 mA are measurable on the 2electrodes on the right, which evidences a current leakage of 13% in thearray including two shielding electrodes. In array C1, 4.246 mA ofcurrent are generated across the 2 electrodes on the left and 0.775 mAare measurable on the 2 electrodes on the right, which evidences acurrent leakage of 18% in the array including 2 non-shieldingelectrodes. In array C2, 4.126 mA of current are generated across the 2electrodes on the left and 0.793 mA are measurable on the 2 electrodeson the right, which evidences a current leakage of 19% in the arrayincluding four non-shielding electrodes. Overall, this experimentconfirms that inclusion of non-shielding electrodes can decrease currentleakage and inclusion of shielding electrodes can significant decreasecurrent leakage between nearby, but not adjacent, stimulationelectrodes. For comparison, use of separate and isolated power supplieswith adjacent electrodes, as in FIGS. 11C and 11D, resulted in a currentleakage of 12% and an identical electrode arrangement using a singlepower supply resulted in a current leakage of 33%.

Various aspects of different embodiments of the present invention areexpressed in paragraphs X1, X2, and X3 as follows:

X1. One aspect of the present invention pertains to a method forproviding optimized neurostimulation, including providing an electrodearray configured to generate at least two simultaneous waveforms, eachwaveform including a frequency, a charge balance time, a phase and atleast one pulse; optimizing at least one of the at least twosimultaneous waveforms to reduce pulse collisions by at least one ofaltering the phase of the waveform, altering the frequency of thewaveform, optimizing the charge balance time of the waveform, delaying apulse of the waveform, and blanking a pulse of the waveform; andactivating the electrode array to generate the at least two simultaneouswaveforms.

X2. Another aspect of the present invention pertains to a method forproviding optimized neurostimulation, including providing an electrodearray comprising a plurality of electrodes, wherein the plurality ofelectrodes are divided into at least two groups of electrodes, andwherein the electrode array is configured to generate at least twosimultaneous waveforms; providing a power source for each group ofelectrodes, each power source being electrically isolated and physicallyseparate from each other power source; and activating the electrodearray to generate the at least two simultaneous waveforms.

X3. A further aspect of the present invention pertains to a method forproviding optimized neurostimulation, including providing an electrodearray comprising a plurality of electrodes; grouping the plurality ofelectrodes into a first group including at least one electrodeconfigured to generate a first waveform, a second group including atleast one electrode configured to generate a second waveform, and athird group including at least one electrode with a fixed potential,wherein the third group is located between the first group and thesecond group; and activating the electrode array to generate at leastone of the first waveform and the second waveform.

Yet other embodiments pertain to any of the previous statements X1, X2,or X3 which are combined with one or more of the following otheraspects.

The method further comprising identifying one of the at least twosimultaneous waveforms as a high priority waveform, and wherein theoptimizing is applied to a waveform other than the high prioritywaveform.

Wherein said optimizing includes at least two of altering the phase ofthe waveform, altering the frequency of the waveform, optimizing thecharge balance time of the waveform, delaying a pulse of the waveform,and blanking a pulse of the waveform.

Wherein optimizing the charge balance time of the waveform includes atleast one of increasing a recharge period, decreasing a recharge period,increasing a shorting period, and decreasing a shorting period.

Wherein optimizing the charge balance time of the waveform includes atleast one of decreasing a recharge period and decreasing a shortingperiod.

The method further comprising transmitting the at least two simultaneouswaveforms to a receiver in communication with a processor, the processorbeing in communication with the electrode array.

Wherein the electrode array is implanted in a patient.

Wherein the transmitting occurs before the activating and after theoptimizing.

Wherein the transmitting occurs before the activating.

Wherein the optimizing occurs before the activating.

Wherein the optimizing occurs before the activating and after thetransmitting.

Wherein each of the at least two simultaneous waveforms includesnon-identical frequencies.

Wherein altering the phase of the waveform includes delaying the phaseof the waveform.

Wherein altering the frequency of the waveform includes increasing ordecreasing the frequency of the waveform.

Wherein, for each group of electrodes, each electrode within the groupshares a common frequency and pulse width.

Wherein the electrode array is implanted in a patent.

Wherein the first group, the second group, and the third group eachinclude at least two electrodes.

The foregoing detailed description is given primarily for clearness ofunderstanding and no unnecessary limitations are to be understoodtherefrom for modifications can be made by those skilled in the art uponreading this disclosure and may be made without departing from thespirit of the invention.

What is claimed is:
 1. A method for providing optimizedneurostimulation, comprising: providing an electrode array comprising aplurality of electrodes, wherein the plurality of electrodes are dividedinto at least two groups of electrodes, and wherein the electrode arrayis configured to generate at least two simultaneous waveforms; providinga power source for each group of electrodes, each power source beingelectrically isolated and physically separate from each other powersource; and activating the electrode array to generate the at least twosimultaneous waveforms.
 2. The method of claim 1, wherein, for eachgroup of electrodes, each electrode within the group shares a commonfrequency and pulse width.
 3. The method of claim 1, wherein theelectrode array is implanted in a patent.
 4. A method for providingoptimized neurostimulation, comprising: providing an electrode arraycomprising a plurality of electrodes; grouping the plurality ofelectrodes into a first group including at least one electrodeconfigured to generate a first waveform, a second group including atleast one electrode configured to generate a second waveform, and athird group including at least one electrode with a fixed potential,wherein the third group is located between the first group and thesecond group; and activating the electrode array to generate at leastone of the first waveform and the second waveform.
 5. The method ofclaim 4, wherein the electrode array is implanted in a patient.
 6. Themethod of claim 4, wherein the first group, the second group, and thethird group each include at least two electrodes.